ONO-4578

Ono Pharmaceutical on Thursday said its Bristol Myers Squibb-partnered oral EP4 antagonist ONO-4578, in combination with the latter’s PD-1 inhibitor Opdivo (nivolumab) and chemotherapy, hit the mark in a mid-stage study, demonstrating a progression-free survival (PFS) benefit in first-line advanced HER2-negative gastric cancer. According to Ono, ONO-4578 is designed to block the PGE2 pathway used by cancer cells to suppress immune responses, with the aim of restoring anti-tumour immunity. Combined with Opdivo, it showed promising activity and manageable safety in an earlier Phase I study involving heavily pretreated patients with gastric cancer. The Phase II ONO-4578-08 study, conducted across Japan, South Korea and Taiwan, enrolled 210 treatment-naïve patients with HER2-negative unresectable advanced or recurrent gastric cancer, including gastroesophageal junction cancer. Participants were randomised to receive either ONO-4578 or placebo, alongside Opdivo plus chemotherapy until disease progression or unacceptable toxicity occurred. Findings showed the study met its primary endpoint, with the ONO-4578-based triplet achieving significantly prolonged PFS compared with placebo plus Opdivo and chemotherapy. Furthermore, no new safety concerns were noted during the trial. Detailed findings will be presented at an upcoming medical conference. Under the the 2017 agreement, the partners will jointly develop and commercialise ONO-4578 in Japan, South Korea and Taiwan, whereas Ono retains exclusive rights in China and ASEAN countries. In all remaining regions, Bristol Myers Squibb solely holds rights to the EP4 antagonist.

Ono Pharmaceutical’s selective prostaglandin E2 receptor 4 antagonist is aimed at targeting immunosuppressive factors in the tumor microenvironment. \n Ono Pharmaceutical’s EP4 antagonist hit the primary progression-free survival endpoint in a phase 2 trial in patients with gastric cancer.The biopharma evaluated the Bristol Myers Squibb-partnered candidate, dubbed ONO-4578, in combination with the PD-1 blocker Opdivo and chemotherapy in patients in Japan, South Korea and Taiwan with HER2-negative unresectable advanced or recurrent gastric cancer or gastroesophageal junction cancer.The study tied this combo treatment regimen to a statistically significant prolongation of progression-free survival when compared to placebo, hitting the trial’s primary endpoint.Ono didn’t share any data in the sparse press release, promising to unveil the findings at future academic meeting.The selective prostaglandin E2 receptor 4 antagonist is aimed at targeting immunosuppressive factors in the tumor microenvironment. Japan-based Ono reaffirmed today that it is conducting several other trials of ONO-4578, including a global phase 2 study in patients with colorectal cancer.Ono codeveloped Opdivo with BMS, and the Japanese biopharma scored its own FDA approval earlier this year for Romvimza to treat a type of noncancerous growth. BMS spotted ONO-4578’s potential back in 2017, when the U.S. pharma paid $40 million upfront for the rights to the drug outside of Japan, South Korea, Taiwan, China and Association of Southeast Asian Nations (ASEAN) countries.Under the terms of that deal, BMS and Ono have partnered on developing ONO-4578 in Japan, South Korea and Taiwan under the two companies’ longstanding collaboration agreement. In China and ASEAN countries, Ono retained the exclusive rights.“To improve long-term outcomes for more patients with cancer, we believe more immuno-oncology based combinations may be required, and we are pleased to continue our long-standing collaboration with Ono with this focus in mind,” BMS explained at the time.